Innate Immunity Part II Flashcards
What are the 3 general steps in Complement Activation?
C3 convertase
C5 convertase
MAC attack complex formation
Explain the role of C3 convertase?
It cleaves C3 into C3a and C3b.
C3a acts in the inflammatory response
C3b becomes covalently attached to microbe= opsonizon for phag promotion.
C3 convertase binds C3b to become C5 convertase.
Explain the role of C5 convertase.
C5 convertase cleaves C5 into C5a and C5b.
C5a promotes changes in permeability of blood vessels.
C5b attaches to microbe and starts the MAC= C6, C7, C8, C9
What are the components of the C3 convertase?
C4bC2a
Explain the classical pathway steps?
Requires IgM or IgG and
C1q bind Fc region of Ab and then C1r,s perform cleavage.
C3 convertase=C4bC2a
C5 convertase= C4bC2aC3b
MAC
Explain the Alternative pathway steps?
Spontaneous/”tickover”
C3 hydrolysis=reason for DAF, CR1, and Fl regulatory proteins
Factor D cleaves Factor B= Ba and Bb
C3bBb bind=then bind C3b of C5 Convertase
Serum protein properdin stabilizes interactions.
C5 convertase
MAC
Explain the steps in the Lectin Pathway?
Triggered by mannose-binding lectin binding terminal mannose residues on microbes.
Binding activates MASP1/2=perform proteolytic cleavage.
C3 convertase
C5 convertase
MAC
What are Collectins?
Collectins are trimeric proteins with Lectin heads
Soluble effector molecules
SP-A and SP-D are collections
Surfactant proteins that can Opsonin microbes for alveolar macrophages and inhibit growth.
What three homologous hexameric proteins can imitate complement?
C1q can when it binds IgM
MBL/MASP1, 2 can when it binds mannose on microbe surface
Ficolin/ MASP1, 2 can when it binds N-acetylglucosamine
What are Ficolins?
Plasma proteins that are structurally similar to Collectins but have fibrinogen-type carbohydrate recognition
Molecular ligands are N-acetylgulcosamine and lipoteichoic acid=gram positive
What is the common component of all three complement pathways? There is one molecule…
C3b
What are the complement regulatory proteins?
DAF= Decay-Accelerating Factor
Blocks C2/C4b interaction or enhance dissociation of C4bC2a
CR1= Complement receptor 1
Enhances dissociation of C4bC2a
F1= Factor 1
With CR1, it cleaves C4b/C3b
What are C3a specific functions?
Vasoaction of mast and basophils cells
What are C4a specific functions?
Increased chemokinesis
PG/ROS/RNS in neutrophils
What C5a specific functions?
Increased IL-I, IL-6
PG
ROS, RNS
Expression of CAMs on monocytes and Macs
What are resident Macrophages activated by?
LPS by TLR
IFN-Gamma binds from NK or T-Cells binds cytokine receptor
Complement fragment
What are resident macrophage functional responses?
Acute Inflammation via TNF, IL-1= leads to IL-6,
Also IL-12
ROS/NOS
phage
Understand local vs. systemic action of cytokines in inflammation.
Systemic TNF can cause
Septic shock, decreased cardiac function, thrombosis and capillary leak, metabolic abnormalities due to insulin resistance.
What are Acute Phase Proteins?
Plasma proteins belonging to the pentraxin family
Examples are C-reactive protein (CRP) and Serum Amyloid P (SAP)
Expression in the liver via IL-6/IL-1 induction
What do E-reactive protein and serum amyloid P recognize?
CRP=phosphoric hotline
SAP=phosphatidylethanolamine
Can activate complement by binding C1q
What are the three complement system cascades? And what are they composed of?
The Classical Pathway
The Alternative Pathway
The Lectin Pathway
They composed of plasma proteins expressed in the liver that at as proteolytic proteases.
